Animal Welfare and Ethics in the Collection of Fetal Blood for the Production of Fetal Bovine Serum April- By Rosemary J. Verstegeen, Jenny Murray, and Steven Doelger


Fetal Bovine Serum – Geographical Origin and International Trade – By Jennifer A. Murray and Rosemary J. Versteegen


CellShip: An Ambient Temperature Transport and Short-Term Storage Medium for Mammalian Cell Cultures –  By Emma Buick, Andrew Mead, Abeer Alhubaysh, Patricia Bou Assi, Parijat Das, James Dayus, Mark Turner, Lukasz Kowalski, Jenny Murray, Derek Renshaw, and Sebastien Farnaud

Citations about the Use of Chick Embryo Extract (CEE) in the Literature


    1. Beurg, M., et al. (1999) Differential Regulation of Skeletal Muscle L-type Ca2+ Current and Excitation-contraction Coupling by the Dihydropyridine Receptor Beta Subunit. Biophys. J., 76(4): 1744-1756.
    2. Bultynck, G., et al. (2001) Characterization and Mapping of the 12kda Fk506-binding Protein (Fkbp12)-binding Site on Different Isoforms of the Ryanodine Receptor and the Inositol 1,4,5-trisphosphate Receptor. Biochem. J., 354: 413-422.
    3. Christman, S. A., et al. (2005) Chicken Embryo Extract Mitigates Growth and Morphological Changes in a Spontaneously Immortalized Chicken Embryo Fibroblast Cell Line. Poultry Science, 84(9):1423–1431.
    4. Erbay, E. and Chen, J. (2001) The Mammalian Target of Rapamycin Regulates C2C12 Myogenesis via a Kinase-Independent Mechanism. J. Biol. Chem., 276(39): 36079-36082.
    5. Hagiwara, Y., et al. (1981) Chick Embryo Extract, Muscle Trophic Factor and Chick and Horse Sera as Environments for Chick Myogenic Cell Growth. Develop., Growth and Differ., 23(3): 249-254 doi:10.1111/j.1440-169X.1981.00249.x
    6. Hennige, A. M., (2008) Fetuin-A Induces Cytokine Expression and Suppresses Adiponectin Production. PLoS One, 3(3): e1765 DOI: 10.1371/journal.pone.0001765.
    7. Jat, P.S., et al. (1991) Direct Derivation of Conditionally Immortal Cell Lines from an H-2Kb-Tsa58 Transgenic Mouse. PNAS, 88(12): 5096-5100.
    8. Kessler, P.D., et al. (1996) Gene Delivery to Skeletal Muscle Results in Sustained Expression and Systemic Delivery of a Therapeutic Protein. PNAS, 93(24): 14082-14087.
    9. Krützfeldt, J., et al. (2000) Insulin Signalling and Action in Cultured Skeletal Muscle Cells From Lean Healthy Humans With High and Low Insulin Sensitivity. Diabetes, 49(6): 992-998.
    10. Lecce, J. G., et al. (1953) Chick Embryo Extract, and Enrichment for Certain Strains of Pleuropneumonia Like Organisms Isolated from Man. J. Bacteriol., 66(5): 622–623.
    11. Kita, K., et al. (1998) Influence Of Chicken Embryo Extract On Protein Synthesis Of Chicken Embryo Depends On Cell Density. AJAS, 11(6): 713-717.
    12. Mann, C.J., et al. (2001) Antisense-Induced Exon Skipping and Synthesis of Dystrophin in the Mdx Mouse. PNAS, 98(1): 42-47.
    13. <Morgan, J.E., et al. (1994) Myogenic Cell Lines Derived from Transgenic Mice Carrying a Thermolabile T Antigen: A Model System for the Derivation of Tissue-Specific and Mutation-Specific Cell Lines. Dev Biol., 162(2): 486-498.
    14. Mu, X., et al. (2013) Chick Embryo Extract Demethylates Tumor Suppressor Genes in Osteosarcoma Cells. Clin Orthop Relat Res., [Epub ahead of print]
    15. Muses, S., et al. (2011) A New Extensively Characterised Conditionally Immortal Muscle Cell-Line for Investigating Therapeutic Strategies in Muscular Dystrophies. PLoS One, 6(9): e24826 DOI: 10.1371/journal.pone.0024826.
    16. Pajtler, K., et al. (2010) Production of Chick Embryo Extract for the Cultivation of Murine Neural Crest Stem Cells. J. Vis. Exp. (45), e2380, doi:10.3791/2380.
    17. Slater, C.R. (1976) Control of Myogenesis In Vitro by Chick Embryo Extract. Dev. Biol., 50(2): 264–284.
    18. Stefan, N., et al. (2007) Genetic Variations in PPARD and PPARGC1A Determine Mitochondrial Function and Change in Aerobic Physical Fitness and Insulin Sensitivity during Lifestyle Intervention. J. Clin. Endocrinol. Metab., 92(5): 1827– 1833.
    19. Suzuki, K., et al. (2001) Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure. Circulation, 18:104 (12 Suppl 1) I213-I217 doi: 10.1161/ hc37t1.094929.
    20. Turbow, M.M. (1966) Trypan Blue Induced Teratogenesis of Rat Embryos Cultivated In Vitro. J. Embryo. Exp. Morphol. 15(3): 387-395.
    21. Weigert, C., et al. (2004) Palmitate, but Not Unsaturated Fatty Acids, Induces the Expression of Interleukin-6 in Human Myotubes through proteasome-dependent Activation of Nuclear Factor-κB. J. Biol. Chem., 279(23): 23942–23952.
    22. Yablonka-Reuveni, Z. (1995) Myogenesis in the Chicken: The Onset of Differentiation of Adult Myoblasts is Influenced by Tissue Factors. Basic and Applied Myology, 5(1):33.
    23. Zimmermann, W. H., et al. (2002) Tissue Engineering of a Differentiated Cardiac Muscle Construct. Circ. Res, 90(2): 223-230 DOI: 10.1161/hh0202.103644.


Citations about the Use of Human AB Serum in the Literature


    1. Cánovas, D., and Bird, N., (2012) Letter: Human AB serum as an alternative to fetal bovine serum for endothelial and cancer cell culture. Altex, 29(4): 426-428.
    2. Chimenti, I., et al. (2014) Serum and supplement optimization for EU GMP-compliance in cardiospheres cell culture. J. Cell. Mol. Med. 18(4): 624–634.
    3. Dahl, J. A., et al. (2008) Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum. Int. J. Dev. Biol., 52(8): 1033–1042.
    4. Jung, S., et al. (2012) Ex Vivo expansion of human mesenchymal stem cells in defined serum-free media. Stem Cells Int., 2012 Article ID 123030, doi:10.1155/2012/123030.
    5. Kocaoemer, A., et al. (2007) Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of Mesenchymal Stem Cells from adipose tissue. Stem Cells, 25(5): 1270-1278.
    6. Le Blanc, K., et al. (2007) Generation of immunosuppressive Mesenchymal Stem Cells in allogeneic Human Serum. Transplantation, 84(8): 1055-1059.
    7. Lindroos, B., et al. (2010) Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng. Part A, 16(7): 2281-2294, DOI: 10.1089/ten.tea.2009.0621.
    8. Paloni, A., et al. (2009) Selection of CD271+ cells and human AB serum allows a large expansion of mesenchymal stromal cells from human bone marrow. Cytotherapy, 11(2): 153-162.
    9. Qasim, W., et al. (2017) Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Science Translational Medicine. 9(374), DOI: 10.1126/scitranslmed.aaj2013
    10. Shahdadfar, A., et al. (2005) In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells, 23(9): 1357–1366.
    11. Stute, N., et al. (2004) Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp. Hematol., 32(12): 1212–1225.


Citations about the Application of hPL in the Literature


    1. Astori, G., et al. (2016) Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future. Stem Cell Research & Therapy. 7:93
    2. Azouna, N. B., et al. (2012) Phenotypical and functional characteristics of mesenchymal stem cells from bone marrow: comparison of culture using different media supplemented with human platelet lysate or fetal bovine serum. Stem Cell Res Ther., 3(1):6.
    3. Barsotti, M. C., et al. (2013) Effect of platelet lysate on human cells involved in different phases of wound healing. PLOS, 8(12): e84753.
    4. Bieback, K., et al. (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cell, 27(9):2331-2341.
    5. Burnouf, T., et al. (2012) Human blood-derived fibrin releasates: Composition and use for the culture. Biologicals, 40: 21-30.
    6. Burnouf, T., et al. (2016) Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials, 76: 371-387.
    7. Capelli, C., et al. (2007) Human Platelet Lysate allows expansion and clinical grade production of mesenchymal stromal cells from small samples of bone marrow aspirates or marrow filter washouts. Bone Marrow Transplant, 40(8):785-791.
    8. Castegnaro, S., et al. (2011) Effect of platelet lysate on the functional and molecular characteristics of mesenchymal stem cells isolated form adipose tissue. Curr Stem Cell Res Ther., 6(2):105-114.
    9. Cholewa, D., et al. (2011) Expansion of adipose mesenchymal stromal cells is affected by human platelet lysate and plating density. Cell Transplant, 20(9):1409-1422.
    10. Doucet, C., et al. (2005) Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol., 205(2):228-236.
    11. Fazzina, R., et al. (2015) Culture of human cell lines by a pathogen-inactivated human platelet lysate. Cytotechnology, DOI 10.1007/s10616-015-9878-5.
    12. Fekete. N., et al. (2012) Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. Cytotherapy, 2012; 14(5):540-554.
    13. Govindasamy, V., et al. (2011) Human platelet lysate permits scale-up of dental pulp stromal cells for clinical applications. Cytotherapy, 13(10):1221-1233.
    14. Hemeda, H., et al. (2013) Heparin concentration is critical for cell culture with human platelet lysate. Cytotherapy, 15(9):1174-1181.
    15. Hemeda, H., et al. (2014) Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells. Cytotherapy, 16(2):170-180.
    16. Henschler, R., et al. (2019) Human platelet lysate current standards and future developments. Transfusion, 9999;1–7. DOI: 10.1111/trf.15174
    17. Horn, P., et al. (2010) Impact of individual platelet lysates on isolation and growth of human mesenchymal stromal cells. Cytotherapy, 12(7):888-898.
    18. Naaijkens, B.A., et al. (2012) Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications. Cell Tissue Res., 348(1):119-130.
    19. Rauch, C., et al. (2011) Alternatives to the use of fetal bovine serum: Human platelet lysates as a serum substitute in cell culture media. ALTEX, 28(4):305-316.
    20. Rauch, C., et al (2014) Human Platelets successfully replace fetal bovine serum in adipose-derived adult stem cell culture. J Advanced Biotech & Bioengineering, 2 (1).
    21. Ruggiu, A., et al. (2013) The effect of Platelet Lysate on osteoblast proliferation associated with a transient increase of the inflammatory response in bone regeneration. Biomaterials, 34: 9318-9330.
    22. Schallmoser, K., et al. (2007) Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion, 47(8):1436-1446.
    23. Schallmoser, K., and Strunk, D. (2009) Preparation of Pooled Human Platelet Lysate (pHPL) as an Efficient Supplement for Animal Serum-Free Human Stem Cell Cultures. Journal of Visualized Experiments,
    24. Strandberg, G., et al. (2016) Standardizing the freeze-thaw preparation of growth factors from platelet lysate. Transfusion DOI:10.1111/trf.13998
    25. Suri, K., et al. (2014) Platelet Lysate as a replacement for fetal bovine serum in limbal stem cell cultures: Preliminary results. Investigative Ophthalmology & Visual Science, 55: 511.
    26. Trojahn Kølle, S.F., et al. (2013) Pooled human platelet lysate versus fetal bovine serum-investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use. Cytotherapy, 15(9):1086-1097.
    27. Walenda, G., et al. (2012) Human platelet lysate gel provides a novel three dimensional-matrix for enhanced culture expansion of mesenchymal stromal cells. Tissue Eng Part C Methods, 18(12):924-934.


Citations about Alternatives to FBS in the literature


    1. Paranjape, S. (2004) Goat serum: an alternative to fetal bovine serum in biomedical research. Indian J Exp Biol. 42(1):26-35.
    2. Dessels, C., et al. (2016) Making the Switch: Alternatives to Fetal Bovine Serum for Adipose-Derived Stromal Cell Expansion. Front Cell Dev Biol. 4:115


Citations about FBS in the Literature


    1. Brown, S., et al (2018) Gamma Irradiation of Animal Serum: Maintaining the old Chain Throughout the Process. Bioprocessing J. Trends & Developments in Bioprocess Technology 17
    2. Cheever, M., Master, A., & Versteegen, R. (2017) A Method for Differentiating Fetal Bovine Serum from Newborn Calf Serum. Bioprocessing J. Trends & Developments in Bioprocess Technology 16.
    3. Croonenborghs, B., et al. (2016) Gamma Irradiation of Frozen Animal Serum: Dose Mapping for Irradiation Process Validation. Bioprocessing J. Trends & Developments in Bioprocess Technology. 15(3).
    4. Davis, D., and Drake Hirschi, S. (2014) Fetal Bovine Serum: What You Should Ask Your Supplier and Why. BioProcessing J. Trends & Developments in BioProcess Technology. 13 (1): 19-21
    5. Hawkes, P.W. (2015) Fetal bovine serum: geographic origin and regulatory relevance of viral contamination. Bioresources and Bioprocessing. 2(34):
    6. Nielsen, O. B., and Hawkes P. W. (2019) Fetal Bovine Serum and the Slaughter of Pregnant Cows: Animal Welfare and Ethics. BioProcessing J. Trends & Developments in Bioprocess Technology. 18
    7. Plavsic, M., et al. (2016) Gamma Irradiation of Animal Serum: Validation of Efficacy for Pathogen Reduction and Assessment of Impacts on Serum Performance. BioProcessing J. Trends & Developments in BioProcess Technology. 15(2):12-21
    8. Siegel, W., and Foster, L. (2013) Fetal Bovine Serum: The Impact of Geography. BioProcessing J. Trends & Developments in BioProcess Technology. 12(3):28-30.
    9. Versteegen, R., et al. (2016) Gamma Irradiation of Animal Serum: An Introduction. BioProcessing J. Trends & Developments in BioProcess Technology. 15 (2):5-11
    10. Versteegen, R. (2017) Serum: A Better Characterized Biological.. American Pharmaceutical Review 20 (5)